In-vitro investigations evaluating the detection spectrum of cervical lymph nodes via handheld gamma probe.
Currently the significance of the sentinel node (SN) biopsy also for head and neck cancer is discussed intensively. Based on the complex anatomic structures of this region with a low distance between primary and sentinel node as well as approximately 300 lymph nodes an intensive discussion of the methodical basis of sentinel node detection seems to be essential. Thus it was the aim of the present study to examine the detection spectrum of a gamma probe for identification of cervical lymph nodes using an in vitro model to describe and objectify the particularities of measurement existing in the head and neck region. In an in vitro model the detection spectrum of a gamma probe is examined in 29 different series of measurements (variation of the specimen filled with 99m pertechnetat regarding activity, position, collimator distance, tissue sheath). The presented in vitro model reflects the clinical problem of narrow intranodal activity of neighbouring lymph nodes and reveals a direct relation between the number of radiation sources and their isolated evidence. Using muscle tissue with a thickness of 0.4 cm, two two-rowed radiation sources, the more powerful is placed 1.5 cm behind the other specimen, with a lateral difference of 3 cm, can be resolved only with a maximal detector distance of 1 cm. Not the difference of the tissue but the thickness of the tissue is decisive for detection. Especially for pharyngeal and laryngeal lymph nodes a transcutaneous measurement reflecting the exact localisation of hot nodes in the area of the deep jugular lymph nodes is not possible with increasing tissue thickness. The described results require a critical discussion of the different detection techniques varying among the different working groups of this field.


Enhanced performance of glycerol electro-oxidation in alkaline media using bimetallic Au-Cu NPs supported by MWCNTs and reducible metal oxides.
Electrochemical technologies for valorizing glycerol, a byproduct of biodiesel production, into electric energy and value-added chemical products continue to be technologically and economically challenging. In this field, an ongoing challenge is developing more active, stable, and low-cost heterogeneous catalysts for the glycerol electro-oxidation reaction (GlyEOR). This paper reports the influence of the preparation procedure, which involves intermatrix synthesis (Cu and Au NPs), followed by galvanic displacement (Cu-Au NPs) in previously functionalized multi-walled carbon nanotubes (MWCNTs). It also discusses the role of the supports, CeO2 NPs, and TiO2 NPs, obtained by a hydrothermal microwave-assisted procedure, on the electroactivity of a hybrid bimetallic Cu-Au/MWCNT/MO2 catalyst in the GlyEOR in alkaline media. The electrocatalytic behavior was studied and discussed in terms of structure, composition, and electroactivity of the synthesized materials, which were determined by Fourier-transform infrared spectroscopy (FTIR), flame atomic absorption spectroscopy (FAAS), transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM), X-ray photoelectronic spectroscopy (XPS), and cyclic voltammetry (CV). In addition, the role of the oxidation states of Cu and Au in the as-prepared catalysts (Cu/MWCNT, Au/MWCNT, Cu-Au/MWCNT, Cu-Au/MWCNT-CeO2, and Cu-Au/MWCNT-TiO2) was demonstrated. It was concluded that the preparation method of metal NPs for the controlled formation of the most catalytically active oxidation states of Cu and Au, together with the presence of a conductive and oxophilic microenvironment provided by carbon nanotubes and facile reducible oxides in optimized compositions, allows for an increase in the catalytic performance of synthesized catalysts in the GlyEOR.


Atomic and electronic structures of an extremely fragile liquid.
The structure of high-temperature liquids is an important topic for understanding the fragility of liquids. Here we report the structure of a high-temperature non-glass-forming oxide liquid, ZrO2, at an atomistic and electronic level. The Bhatia-Thornton number-number structure factor of ZrO2 does not show a first sharp diffraction peak. The atomic structure comprises ZrO5, ZrO6 and ZrO7 polyhedra with a significant contribution of edge sharing of oxygen in addition to corner sharing. The variety of large oxygen coordination and polyhedral connections with short Zr-O bond lifetimes, induced by the relatively large ionic radius of zirconium, disturbs the evolution of intermediate-range ordering, which leads to a reduced electronic band gap and increased delocalization in the ionic Zr-O bonding. The details of the chemical bonding explain the extremely low viscosity of the liquid and the absence of a first sharp diffraction peak, and indicate that liquid ZrO2 is an extremely fragile liquid.


Smoking as a risk factor for the development of arterial occlusive disease.
There was examined a total of 982 males with arterial occlusive disease (908 males with atherosclerosis obliterans, 59 with thromboangitis obliterans and 15 males with this disease of uncertain aetiology), 30 females with atherosclerosis obliterans, 411 control males and 50 control females. Among the controls there were significantly more frequently non-smokers and occasional smokers (the latter, however, having atherosclerosis obliterans--with the exception of females, and males having thromboangitis obliterans). In the complex of occlusive disease there were, on the other hand, more frequently present regular smokers smoking 31-40 years (in thromboangiitics for a period up to 10 years), smoking proportionally throughout the day and having their starting age of smoking before their 20th year of life. In the group of the arterial occlusive disease there was also a significantly higher number of those who discontinued smoking for 1-2 years in their life, while in the control group there were chiefly males who had discontinued smoking for a period longer than 5 years. Among stop-smokers there occurred significantly more frequently patients having only occlusions and significantly less frequently those having both occlusions and stenoses. There were no significant differences between the group with a pathological arterial process and the control one in the prevalence of cigar smokers or in the existence of their different smoking habits. The situation was similar also with pipe smokers with one exception: in the occlusive disease and/or atherosclerosis obliterans there were found more frequently mixed smokers of more than one package of tobacco weekly, smoking 31-40 years, namely proportionally throughout the day. As significant there proved to be chiefly cigarette smoking, and that in the amount over 16 cigarettes a day. As critical was found to be the period of exposition of 31-40 years. But when the relationship between the average daily number of cigarettes smoked and the total duration of smoking was compared, there was found in males with atherosclerosis obliterans as significant the smoking of already 11-15 cigarettes a day for a period of 31-40 years. With the rising number of cigarettes smoked per day there was getting shorter the critical period of exposition. Of importance is likewise the starting age of cigarette smoking before the 20th year of life and the proportional time distribution of smoking in the course of the whole day. In the complex of the arterial occlusive disease there were significantly more "rapid" smokers, i.e. those smoking their cigarette within a time up to 6 minutes and, further, those in whom, 5-8 years prior to the onse


[Conditions of metastatic spread of endometrial cancer: analysis of autopsy findings and clinical data].
Among 263 patients who suffered from endometrial carcinoma and died of their disease or unrelated causes autopsies showed metastases or recurrences in 165 cases. The conditions for metastatic spread were analysed from the morphological parameters of the tumour. The incidence and localization of above all the lymph node metastases are closely correlated to the grading and the depth of invasion (I 0 to I 3/3) of the primary tumour. The incidence of pelvic lymph node metastases is 8.7% at an invasion depth I 1/3,33% at an invasion depth of I 3/3 of the myometrium. Tumours with the invasion depth I 1/3 show metastases in the para-aortic lymph nodes in 17.3% and at the invasion depth I 3/3 in 50% of the cases. At an invasion depth of I 3/3 17% had exclusively para-aortic lymph node metastases. Pelvic lymph node metastases were found in tumours of the grading G 1 in 5.7% of the cases, in grading G3 in 26% of the cases. The tumour grading and primary extent of the endometrial carcinoma area are closely correlated. At a grading G1 90% of the cases were in stage I/II and only 10% in stage III/or IV. At a grading G3 23.8% of the cases were stage I/II and 76.2% of the cases stage III/IV. Based on the presented analysis it is recommended to supplement the conventional treatment at an invasion depth I 2/3 of I 3/3 with radiotherapy of the para-aortic lymph nodes since 27.3 to 50% of these cases show para-aortic metastases. In 17% of the endometrial carcinomas with an invasion depth I 3/3 exclusively para-aortic lymph node metastases were found which do not respond to conventional treatment.


Improved coagulation and haemostasis in haemophilia with inhibitors by combinations of superFactor Va and Factor VIIa.
Bypassing inhibitors in haemophilia patients is limited to activated (a) Factor(F)VII products. We introduced "FVa activity augmentation" as another bypassing strategy and studied effects of an engineered FVa variant designated superFVa. Procoagulant and clot stabilising properties of superFVa and recombinant human (rh)FVIIa, either alone or in combination, were studied in thrombin generation and clot lysis assays in normal human plasma (NHP) with or without anti-FVIII inhibitors, in haemophilia plasma, and in FVIII-deficient mice or in wild-type mice with anti-FVIII inhibitors. SuperFVa was as effective as rhFVIIa to improve thrombin generation or clot lysis. Furthermore, procoagulant effects were significantly enhanced when these compounds were combined. RhFVIIa at 40 nM (a therapeutic concentration) improved thrombin generation mildly, but markedly improved thrombin generation when combined with a low concentration (e. g. 3 nM) of superFVa. In clot lysis studies, the concentration of rhFVIIa to normalise clot lysis times could be reduced by 100-fold (e. g. from 40 nM to 0.4 nM) when combined with a low concentration (0.37 nM) of superFVa. In haemostasis studies of FVIII-deficient mice, blood loss was dose-dependently reduced by either superFVa or rhFVIIa. SuperFVa (200 U/kg) corrected mean blood loss indistinguishably from rhFVIII. Blood loss correction by rhFVIIa was greatly improved when combined with superFVa. Similar blood loss correction results were observed for therapies in wild-type mice after infusion with anti-FVIII inhibitors. Thus, superFVa may be an effective procoagulant agent in the setting of haemophilia with inhibitors and it merits further evaluation for new bypassing strategies.


Immunoglobulins on the surface of monosodium urate crystals: an immunoelectron microscopic study.
The ability of monosodium urate (MSU) crystals to bind immunoglobulins from human serum was investigated by immunoelectron microscopy. Synthetic MSU crystals were incubated with serum and then processed with an indirect immunoperoxidase technique which used primary antibodies directed against human IgG, IgA or IgM, respectively specific for Fc fragments, alpha chains, and mu chains. Results were analyzed by transmission electron microscopy on intact crystals dried on formvar coated grids, and in thin sections. Both techniques demonstrated the binding of IgG, IgA and IgM to MSU crystals and the availability of the Fc fragment of the crystal bound IgG for immunologic reactions.


Significance of serum immunoglobulin levels in conglomeration with trans-sternal phlebography in the phlebography management of breast cancer.
The study was conducted on 63 patients with breast lump and twenty normal healthy females. In benign breast disease, a significant (P < 0.001) rise in serum IgA, significant (P < 0.001) decrease in IgG and no change in IgM levels was seen before operation. A significant decrease (P < 0.001) in serum IgA and significant increase in IgG and IgM was observed post operatively. In carcinoma breast, a significant (P < 0.001) elevation in IgA, IgG and IgM levels was found pre-operatively with a concomitant decrease in serum IgA and IgG and increase in serum IgM levels, post operatively. Trans-sternal phlebography (TSP) carried out with 95.23% success has revealed significant (P < 0.001) change in the staging of carcinoma breast. The increased levels of serum immunoglobulins associated with the patients of carcinoma breast with metastasis has led to conclude that these levels, if punctuated with TSP findings can lead to better assessment of the staging of carcinoma breast and thereby its management.


Who are the beneficiaries?
Is it defensible that society spends money on medical or research projects intended to help people solve their fertility problems? Suppose that we want to answer this question from the point of view of a utilitarian cost-benefit analysis. The answer to the question then depends, of course, on how expensive these projects turn out to be, relative to the costs of other possible projects. But it depends also on how we assess the benefits of these projects. To whom do they accrue? Who are the beneficiaries of these projects?


Techniques of Sleeve Gastrectomy and Modified Roux-en-Y Gastric Bypass in Mice.
Obesity is a major public health issue, with a prevalence of 4 to 28% for men and 6.2 to 36.5% for women in Europe (from 2003 to 2008). Morbid obesity is frequently associated with metabolic complications, such as type 2 diabetes, hypertension, and dyslipidemia, reducing life expectancy and quality. In the absence of any effective noninvasive treatments, bariatric surgery is a valuable therapeutic option for patients with morbid obesity (body mass index (BMI) >40 kg/m2), leading to long-term, sustained weight loss and improvements in metabolic complications. However, the underlying cellular and molecular mechanisms sustaining the beneficial effects of bariatric surgery are not yet fully understood. Due to the numerous genetically-modified strains available, the mouse model is the most convenient animal model to explore the molecular mechanisms behind the pleiotropic beneficial effects of bariatric surgeries. Here, we detailed the optimized healthcare methods and surgical protocols in mice for the two most widely-used bariatric surgeries: the sleeve gastrectomy and the modified Roux-en-Y gastric bypass. Deciphering the molecular mechanisms underlying the therapeutic effects of bariatric surgeries offers the promise of identifying new therapeutics targets.


In vitro antioxidant activity of Ficus carica L. latex from 18 different cultivars.
As synthetic antioxidants that are widely used in foods are known to cause detrimental health effects, studies on natural additives as potential antioxidants are becoming increasingly important. In this work, the total phenolic content (TPC) and antioxidant activity of Ficus carica Linn latex from 18 cultivars were investigated. The TPC of latex was calculated using the Folin-Ciocalteu assay. 1,1-Diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP) were used for antioxidant activity assessment. The bioactive compounds from F. carica latex were extracted via maceration and ultrasound-assisted extraction (UAE) with 75% ethanol as solvent. Under the same extraction conditions, the latex of cultivar 'White Genoa' showed the highest antioxidant activity of 65.91% ± 1.73% and 61.07% ± 1.65% in DPPH, 98.96% ± 1.06% and 83.04% ± 2.16% in ABTS, and 27.08 ± 0.34 and 24.94 ± 0.84 mg TE/g latex in FRAP assay via maceration and UAE, respectively. The TPC of 'White Genoa' was 315.26 ± 6.14 and 298.52 ± 9.20 µg GAE/mL via the two extraction methods, respectively. The overall results of this work showed that F. carica latex is a potential natural source of antioxidants. This finding is useful for further advancements in the fields of food supplements, food additives and drug synthesis in the future.


Patient Preference for Transradial Access over Transfemoral Access for Cerebrovascular Procedures.
Shared decision-making, when physicians and patients collaborate and agree on health care decisions, is a key tenant of patient-centered care. Choice of access site for neurovascular procedures is rarely a shared decision point between physicians and patients. We present our initial evaluation of patient preference for radial over femoral access for cerebrovascular procedures. IRB approved single-center, prospective, and consecutive survey of all patients undergoing transradial access for cerebrovascular imaging and intervention. Primary inclusion criteria were patients who had previously undergone a transfemoral access procedure and chose to have their second procedure via a transradial approach. All patients underwent pre-procedural neurologic and extremity exams (including Barbeau tests for radial access suitability prior to radial access), post-procedural neurological evaluation and radial access assessment post-procedure, and complete neurological and radial access-site evaluation in the neurointerventional outpatient clinic 1-2 week post-procedure. Twenty five consecutive patients who underwent radial access cerebrovascular procedures after previous femoral access cerebrovascular procedures (16 diagnostic angiograms and 9 interventional procedures) were included. No major complications (including hematomas, infection, or delayed radial artery occlusion) were encountered during the immediate post-procedurral period or on outpatient follow-up (average 8 days). On immediate post-procedural examination, 16% had mild bruising and 24% had mild pain at the radial access site. Of the 25 patients included in this study, 24 strongly preferred radial access over femoral access and reported that, if they needed another procedure, they would prefer radial access. There was nearly unanimous patient preference for radial over femoral access for cerebrovascular procedures in this single-center prospective analysis. There were no major complications and no incidences of delayed radial occlusion. In the current age of value-based and patient-centered medicine, the radial approach should be considered for nearly all neurovascular procedures.


Tissue plasminogen activator in cardiac arrest with pulseless electrical activity.
Coronary thrombosis and pulmonary thromboembolism are common causes of cardiac arrest. We assessed whether the administration of tissue plasminogen activator (t-PA) during cardiopulmonary resuscitation would benefit patients with cardiac arrest and pulseless electrical activity of unknown or presumed cardiovascular cause. Patients who were older than 16 years of age and who had more than one minute of pulseless electrical activity that was unresponsive to initial therapy outside the hospital or in the emergency department were eligible. Patients were randomly assigned to receive 100 mg of t-PA or placebo intravenously over a 15-minute period in a double-blind fashion. Standard resuscitation was then continued for at least 15 minutes. The primary outcome was survival to hospital discharge. During the study period, 1583 patients with cardiac arrest were treated and 233 patients were enrolled (117 in the t-PA group and 116 in the placebo group). The characteristics of the patients in the two groups were similar. One patient in the t-PA group survived to hospital discharge, as compared with none in the placebo group (absolute difference between groups, 0.9; 95 percent confidence interval, -2.6 to 4.8; P=0.99). The proportion of patients with return of spontaneous circulation was 21.4 percent in the t-PA group and 23.3 percent in the placebo group (absolute difference between groups, -1.9; 95 percent confidence interval, -12.6 to 8.8; P=0.85). We found no evidence of a beneficial effect of fibrinolysis in patients with cardiac arrest and pulseless electrical activity of unknown or presumed cardiovascular cause. Our study had limited statistical power, and it remains unknown whether there is a small treatment effect or whether selected subgroups may benefit.


Effects of consent form information on self-disclosure.
When researchers encounter preexisting psychological distress in participants, ethical codes provide little guidance on how to balance issues of beneficence and autonomy. Although researchers may inform participants what will occur given responses indicating distress, this information may lead to biased self-reports. This important issue was addressed in this study by manipulating consent form information regarding the type of psychopathology to be assessed and various levels of possible follow-up. In comparing responses on self-report measures of anxiety, depression, and general psychological distress, men who believed depression was the focus of the study reported fewer symptoms of depression and less trait anxiety as intrusiveness of experimenter follow-up increased. These results are discussed within the framework of socialization theory. Given that half of the sample did not correctly answer questions regarding information contained in the consent form, guidelines to improve consent form comprehension are offered.


Development of a multiplex real-time PCR assay for phylogenetic analysis of Uropathogenic Escherichia coli.
Uropathogenic Escherichia coli (UPEC) is among major pathogens causing 80-90% of all episodes of urinary tract infections (UTIs). Recently, E. coli strains are divided into eight main phylogenetic groups including A, B1, B2, C, D, E, F, and clade I. This study was aimed to develop a rapid, sensitive, and specific multiplex real time PCR method capable of detecting phylogenetic groups of E. coli strains. This study was carried out on E. coli strains (isolated from the patient with UTI) in which the presence of all seven target genes had been confirmed in our previous phylogenetic study. An EvaGreen-based singleplex and multiplex real-time PCR with melting curve analysis was designed for simultaneous detection and differentiation of these genes. The primers were selected mainly based on the production of amplicons with melting temperatures (Tm) ranging from 82°C to 93°C and temperature difference of more than 1.5°C between each peak.The multiplex real-time PCR assays that have been developed in the present study were successful in detecting the eight main phylogenetic groups. Seven distinct melting peaks were discriminated, with Tm value of 93±0.8 for arpA, 89.2±0.1for chuA, 86.5±0.1 for yjaA, 82.3±0.2 for TspE4C2, 87.8±0.1for trpAgpC, 85.4±0.6 for arpAgpE genes, and 91±0.5 for the internal control. To our knowledge, this study is the first melting curve-based real-time PCR assay developed for simultaneous and discrete detection of these seven target genes. Our findings showed that this assay has the potential to be a rapid, reliable and cost-effective alternative for routine phylotyping of E. coli strains.


Case management service quality and patient-centered care.
Providing care that is patient-centered is an important objective in the modern healthcare industry. Despite this objective, hospital inpatient case managers and the services they provide are evaluated routinely without including patients' perspectives. Therefore, the purpose of this study is to fill this research gap by using patient expectations and perceptions to assess the overall quality of and patient satisfaction with hospital case management services. This paper investigates five dimensions of case management services - reliability, responsiveness, assurance, empathy and tangibles - and how they affect overall quality and patient satisfaction. Study surveys are based on the SERVQUAL instrument. Survey data from a cross-sectional sample of 67 inpatients are analyzed using principal component analysis, confirmatory factor analysis, GAP analysis and a predictive model. The preliminary part of the study identifies "tangibles" and "nontangibles" - reliability, responsiveness, assurance and empathy - as the main components. Among these two components, only nontangibles have a positive and significant effect on both quality and patient satisfaction according to patient perspectives. GAP analysis indicates that gaps between patient expectations and perceptions of reliability and assurance are significant. Finally, the proposed predictive model reveals that gaps in assurance have a significant impact on both overall quality and satisfaction, while gaps in empathy have a significant impact on satisfaction, but not overall quality. Studies on service quality at the case manager level are limited. This study is the first in this domain to evaluate quality and satisfaction from the patient perspective.


[Identification of HLA class Ⅱ susceptible alleles and genotypes in latent autoimmune diabetes in adults].
Objective: To identify human leukocyte antigen (HLA)-DRB1, DQA1 and DQB1 susceptible alleles and genotypes in latent autoimmune diabetes in adults (LADA) patients of Chinese Han nationality. Methods: All subjects including 652 LADA patients and 1 181 healthy controls from 1999 to 2015 in Han nationality region of Hunan province were genotyped with high resolution at HLA-DRB1, DQA1 and DQB1 locus by PCR-sequence based typing (PCR-SBT). Frequencies of genotypes between patients and controls were compared by chi square test. Results: The DQA1 susceptible allele was DQA1*03 (OR=1.23, P(c)=0.028); the DQB1 susceptible alleles were DQB1*0201 (OR=2.24, P(c)<0.001), DQB1*0303 (OR=1.30, P(c)=0.030), DQB1*0304 (OR=10.23, P(c)=0.004) and DQB1*0401(OR=1.94, P(c)<0.001); and the DRB1 susceptible alleles were DRB1*0301 (OR=2.10, P(c)<0.001), DRB1*0405(OR=1.89, P(c)<0.001) and DRB1*0901(OR=1.36, P(c)=0.008), respectively in Chinese Han nationality LADA patients. The HLA-Ⅱ susceptible genotypes were DQA1*03/05 (OR=1.81, P(c)=0.007), DQB1*0201/0201(OR=5.74, P(c)<0.001), DQB1*0201/0303 (OR=2.58, P(c)=0.010), DRB1*0301/0901(OR=3.43, P(c)=0.028) and DRB1*0901/0901 (OR=1.82, P(c)=0.021), respectively in LADA patients. DQB1*0201 and DRB1*0301 were shared susceptible alleles for Chinese Han and Caucasian LADA patients, while DQA1*03, DQB1*0303, DQB1*0304, DQB1*0401, DRB1*0405 and DRB1*0901 were specific susceptible alleles for Chinese Han LADA patients. Interestingly, the DQB1*0303 allele was susceptible in Chinese while protective in Caucasian (OR: 1.30 vs 0.29). Conclusion: Susceptible alleles are DQA1*03, DQB1*0201, DQB1*0303, DQB1*0304, DQB1*0401, DRB1*0301, DRB1*0405 and DRB1*0901, and susceptible genotypes are DQA1*03/05, DQB1*0201/0201, DQB1*0201/0303, DRB1*0301/0901 and DRB1*0901/0901 in Chinese LADA patients.


In elderly patients with lung cancer is resection justified in terms of morbidity, mortality and residual quality of life?
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: In [patients over 70 years of age with lung cancer] is [lung resection] when compared with [non-surgical treatment] justified in terms of [postoperative morbidity, mortality and quality of life]? Altogether more than 297 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that patients over 70 years of age undergoing anatomical lung resection respond as well as younger patients in terms of morbidity, mortality and residual quality of life (QoL). Collective analysis of the papers reveals no significant difference in five-year survival rates following surgery for early stage disease (stage I non-small cell lung cancer: <70 years; 69-77%, >70 years; 59-78%), although, elderly patients currently receive far higher rates of palliative care (30-47% in patients 65-70 years vs. 8% in patients under 65 years). Additionally, 30-day mortality rates (5.7% <70 years vs. 1.3-3.3% >70 years), length of hospital stay [1.3 days vs. 1 day (video-assisted mini-thoracotomy) and 4.6 vs. 4.9-5.2 days (thoracotomy) for <70 years vs. >70 years, respectively] and postoperative lung function tests (FEV(1) decrease; 13% <70 years vs. 18% >70 years P=0.34, functional vital capacity decrease; 9% <70 years vs. 14% >70 years P=0.31) are equivalent between the two age groups. Residual QoL following lobectomy (evaluated by patient self-assessment) showed decreased social (P<0.001) and role (P<0.001) functioning but less pain at discharge (P<0.001) in those over 70 years. Global QoL, however, was not influenced by age (global QoL; <70 years 22.2+/-25.3 vs. >70 years 17.6+/-22.9). Pneumonectomy showed statistically significant decreases in physical functioning [six months postoperatively (MPO) P=0.045], role functioning (3 MPO P=0.035), social functioning (6 MPO P=0.006, 12 MPO P=0.001) and general pain (6 MPO P=0.037), but showed no age related differences (<70 years; 81.9+/-19.1, >70 years; 78.0+/-22.8).


Requirements for a Stable Long-Term Result in Surgical Reduction of Vertebral Fragility Fractures.
Osteoporotic vertebral fractures are one of the major health problems in the world. Minimally invasive surgical treatment has great advantages compared with conservative treatment in treating these fractures, because it eliminates pain and functional disability. The percutaneous intravertebral expandable titanium device SpineJack (Vexim SA, Balma, France) is beneficial compared with other kyphoplasty devices, showing results that are maintained over time and a reduction in complications. However, controversy exists about the minimum amount of cement that should be used to achieve long-term restoration and which is essential to minimize complications. We reviewed publications studying the maintenance of long-term restoration using this percutaneous expandable titanium device in cadavers. In this study, we show the first long-term work with patients treated with percutaneous expandable titanium device, describing precise indications concerning the minimum amount of cement that should be used. Results were evaluated from a clinical study including 178 patient outcomes with long-term follow-up results performed by our team. The mean total quantity of cement injected was 4.4 mL (25% vertebral body filling). The leakage rate was 12.9%, and all of these occurrences were asymptomatic. The mean follow-up time was 77 months (60-96 months). All clinical scales improved significantly after the procedure. A recollapse of the treated vertebra was observed in 3 cases (1.6%), and the adjacent fracture rate was 2.2%. From the results of our study and review of the literature, cement equivalent to 25% of the vertebral body filling volume, when combined with the titanium expandable device, seems to be sufficient to prevent recollapse in osteoporotic and type A.3 fractures.


[Gemini surfactants as gene carriers].
Gemini surfactants are a new class of amphiphilic compounds built from two classic surfactant moieties bound together by a special spacer group. These compounds appear to be excellent for creating complexes with DNA and are effective in mediating transfection. Thanks to their construction, DNA carrier molecules built from gemini surfactants are able to deliver genes to cells of almost any DNA molecule size, unattainable when using viral gene delivery systems. Moreover, they are much safer for living organisms.


BRD4 bimodal binding at promoters and drug-induced displacement at Pol II pause sites associates with I-BET sensitivity.
Deregulated transcription is a major driver of diseases such as cancer. Bromodomain and extra-terminal (BET) proteins (BRD2, BRD3, BRD4 and BRDT) are chromatin readers essential for maintaining proper gene transcription by specifically binding acetylated lysine residues. Targeted displacement of BET proteins from chromatin, using BET inhibitors (I-BETs), is a promising therapy, especially for acute myeloid leukemia (AML), and evaluation of resistance mechanisms is necessary to optimize the clinical efficacy of these drugs. To uncover mechanisms of intrinsic I-BET resistance, we quantified chromatin binding and displacement for BRD2, BRD3 and BRD4 after dose response treatment with I-BET151, in sensitive and resistant in vitro models of leukemia, and mapped BET proteins/I-BET interactions genome wide using antibody- and compound-affinity capture methods followed by deep sequencing. The genome-wide map of BET proteins sensitivity to I-BET revealed a bimodal pattern of binding flanking transcription start sites (TSSs), in which drug-mediated displacement from chromatin primarily affects BRD4 downstream of the TSS and prolongs the pausing of RNA Pol II. Correlation of BRD4 binding and drug-mediated displacement at RNA Pol II pause sites with gene expression revealed a differential behavior of sensitive and resistant tumor cells to I-BET and identified a BRD4 signature at promoters of sensitive coding and non-coding genes. We provide evidence that I-BET-induced shift of Pol II pausing at promoters via displacement of BRD4 is a determinant of intrinsic I-BET sensitivity. This finding may guide pharmacological treatment to enhance the clinical utility of such targeted therapies in AML and potentially other BET proteins-driven diseases.


Booster dose of BNT162b2 in a CoronaVac primary vaccination protocol improves neutralization of SARS-CoV-2 Omicron variant.
The emergence of the new SARS-CoV-2 Omicron variant, which is known to accumulate a huge number of mutations when compared to other variants, brought to light the concern about vaccine escape, especially from the neutralization by antibodies induced by vaccination. In this scenario, we evaluated the impact on antibody neutralization induction, against Omicron variant, by a booster dose of BNT162b2 mRNA vaccine after the CoronaVac primary vaccination scheme. The percentage of seroconverted individuals 30 and 60 days after CoronaVac scheme was 17% and 10%, respectively. After booster dose administration, the seroconvertion rate increased to 76.6%. The neutralization mean titer against Omicron in the CoronaVac protocol decreased over time, but after the booster dose, the mean titer increased 43.1 times, indicating a positive impact of this vaccine combination in the serological immune response.


Etoposide-induced cell cycle delay and arrest-dependent modulation of DNA topoisomerase II in small-cell lung cancer cells.
As an approach to the rational design of combination chemotherapy involving the anti-cancer DNA topoisomerase II poison etoposide (VP-16), we have studied the dynamic changes occurring in small-cell lung cancer (SCLC) cell populations during protracted VP-16 exposure. Cytometric methods were used to analyse changes in target enzyme availability and cell cycle progression in a SCLC cell line, mutant for the tumour-suppressor gene p53 and defective in the ability to arrest at the G1/S phase boundary. At concentrations up to 0.25 microM VP-16, cells became arrested in G2 by 24 h exposure, whereas at concentrations 0.25-2 microM G2 arrest was preceded by a dose-dependent early S-phase delay, confirmed by bromodeoxyuridine incorporation. Recovery potential was determined by stathmokinetic analysis and was studied further in aphidicolin-synchronised cultures released from G1/S and subsequently exposed to VP-16 in early S-phase. Cells not experiencing a VP-16-induced S-phase delay entered G2 delay dependent upon the continued presence of VP-16. These cells could progress to mitosis during a 6-24 h period after drug removal. Cells experiencing an early S-phase delay remained in long-term G2 arrest with greatly reducing ability to enter mitosis up to 24 h after removal of VP-16. Irreversible G2 arrest was delimited by the induction of significant levels of DNA cleavage or fragmentation, not associated with overt apoptosis, in the majority of cells. Western blotting of whole-cell preparations showed increases in topoisomerase II levels (up to 4-fold) attributable to cell cycle redistribution, while nuclei from cells recovering from S-phase delay showed enhanced immunoreactivity with an anti-topoisomerase II alpha antibody. The results imply that traverse of G1/S and early S-phase in the presence of a specific topoisomerase II poison gives rise to progressive low-level trapping of topoisomerase II alpha, enhanced topoisomerase II alpha availability and the subsequent irreversible arrest in G2 of cells showing limited DNA fragmentation. We suggest that protracted, low-dose chemotherapeutic regimens incorporating VP-16 are preferentially active towards cells attempting G1/S transition and have the potential for increasing the subsequent action of other topoisomerase II-targeted agents through target enzyme modulation. Combination modalities which prevent such dynamic changes occurring would act to reduce the effectiveness of the VP-16 component.


Vomiting and aspiration of gastric contents: a possible life-threatening combination in underwater diving.
Vomiting and aspiration of gastric contents into the airways and lungs is a common and well-known clinicopathological entity. This phenomenon might also occur in underwater diving, where it can lead to life-threatening or fatal situations. This article presents two incidents involving diving-related vomiting with associated aspiration of gastric contents. One case, a 39-year-old commercial diver using a full-face diving mask, was fatal and the other was a 33-year-old, female recreational scuba diver in whom underwater vomiting was complicated by pulmonary aspiration of a solid foreign body (a peanut) into the right lower lobe bronchus. The peanut was successfully removed and, following bronchoscopic pulmonary lavage, the patient made an uneventful recovery. The causes and consequences of nausea and vomiting within the underwater environment are discussed and possible interpretative problems are highlighted.


Synthesis of Hybrid Reduced Graphene Oxide Decorated with Ru(bpy)3(2+)-Doped Silica Nanoparticles.
Hybrid materials consisting of electrically conductive reduced graphene oxide (RGO) and Ru(bpy)3(2+)-doped silica (Ru@SiO2) nanoparticles were synthesized by hydrolysis of TEOS in the presence of Ru(bpy)3Cl2 and RGO. Many spherical Ru@SiO2 nanoparticles, of an average size of 96 nm, were observed to be strongly anchored on a planar RGO surface in SEM and TEM images. FTIR and EDS analyses confirmed the chemical compositions and functional groups of Ru@SiO2 and partially reduced RGO. The RGO prepared by 200 degrees C thermal treatment of GO in N2 was probed to have a multilayered sheet structure by XRD. An absorption spectrum of the hybrid exhibited a considerable red-shift in the characteristic visible peak of free Ru(bpy)3(2+) centered at 452 nm due to electrostatic interactions between Ru(bpy)3(2+) and negatively charged silica, indicating strong immobilization of Ru(bpy)3(2+) in the silica matrix.


[A case of primary epiploic appendagitis of the sigmoid colon diagnosed by abdominal CT and managed conservatively].
A 40-year-old man presented to our department with left lower abdominal pain. Laboratory test showed slight leukocytosis and moderately elevated C-reactive protein (CRP). Computed tomography (CT) of the abdomen showed a typical fat density lesion adjacent to the sigmoid colon. The diagnosis of primary epiploic appendagitis of the sigmoid colon was established, and the patient was managed conservatively. Primary epiploic appendagitis is a self-limiting illness, and diagnosed by characteristic radiographic findings. Inaccurate diagnosis can lead to unnecessary treatments including surgical intervention. When we encounter a case of acute abdomen, we should consider the possibility of this disease to make accurate diagnosis and give proper treatment.


Mitochondrial-derived vesicles retain membrane potential and contain a functional ATP synthase.
Vesicular transport is a means of communication. While cells can communicate with each other via secretion of extracellular vesicles, less is known regarding organelle-to organelle communication, particularly in the case of mitochondria. Mitochondria are responsible for the production of energy and for essential metabolic pathways in the cell, as well as fundamental processes such as apoptosis and aging. Here, we show that functional mitochondria isolated from Saccharomyces cerevisiae release vesicles, independent of the fission machinery. We isolate these mitochondrial-derived vesicles (MDVs) and find that they are relatively uniform in size, of about 100 nm, and carry selective protein cargo enriched for ATP synthase subunits. Remarkably, we further find that these MDVs harbor a functional ATP synthase complex. We demonstrate that these vesicles have a membrane potential, produce ATP, and seem to fuse with naive mitochondria. Our findings reveal a possible delivery mechanism of ATP-producing vesicles, which can potentially regenerate ATP-deficient mitochondria and may participate in organelle-to-organelle communication.


Mitral valve regurgitation after atrial septal defect repair in adults.
Mitral valve regurgitation (MR) is known to deteriorate following adult atrial septal defect (ASD) repair in the mid to long-term. The study aim was to identify the risk factors for this deterioration. Between 1995 and 2011, a total of 93 consecutive patients (aged > or = 18 years) underwent ASD repair at the authors' institution. Patients who underwent concomitant procedures, other than tricuspid annuloplasty or maze procedure, were excluded; hence, 74 patients were enrolled in the study. MR was evaluated by transthoracic echocardiography shortly after surgery and subsequently on a regular basis in the outpatient clinic. Risk factors for the deterioration of MR were estimated using Cox proportional hazards regression. The mean patient age at surgery was 48.0 +/- 17.1 years, and 20 patients (27%) had atrial fibrillation (AF) preoperatively. The mean follow up was 6.9 +/- 5.5 years. The degree of MR was not unchanged or not improved in 54 patients (73.0%) (group 1), but was increased by one grade in 12 patients (16.2%) (group 2), and by two or more grades in eight patients (10.8%) (group 3). At surgery, all patients in group 3 were aged > 50 years. In group 3, on echocardiography, the average end-diastolic left ventricular dimension was increased from 41.8 mm to 51.8 mm (p = 0.027), and enlargement of the mitral annulus was noted in seven patients. Four of the group 3 patients required reoperation for MR after ASD repair. The Cox proportional hazards model revealed preoperative AF (p = 0.045, hazard ratio (HR): 11.68, 95% confidence interval (95% CI): 1.05-129.48) and Qp/Qs > or = 2.8 (p = 0.015, HR: 9.19, 95% CI :1.53-55.04) to be independent risk factors of new-onset or aggravated MR (by two or more grades) after ASD repair. An earlier repair of ASD would be preferable in terms of MR aggravated after ASD repair. For elderly patients with a preoperative high Qp/Qs and AF, mitral valve annuloplasty with ASD repair should considered.


Topographic representation of tone intensity along the isofrequency axis of cat primary auditory cortex.
The sound pressure level (SPL), henceforth termed intensity, of acoustic signals is encoded in the central auditory system by neurons with different forms of intensity sensitivity. However, knowledge about the topographic organization of neurons with these different properties and hence about the spatial representation of intensity, especially at higher levels of the auditory pathway, is limited. Here we show that in the tonotopically organized primary auditory cortex (AI) of the cat there are orderly topographic organizations, along the isofrequency axis, of several neuronal properties related to the coding of the intensity of tones, viz. minimum threshold, dynamic range, best SPL, and non-monotonicity of spike count--intensity functions to tones of characteristic frequency (CF). Minimum threshold, dynamic range, and best SPL are correlated and alter periodically along isofrequency strips. The steepness of the high-intensity descending slope of spike count--intensity functions also varies systematically, with steepest slopes occurring in the regions along an isofrequency strip where low thresholds, narrow dynamic ranges and low best SPLs are found. As a consequence, CF-tones of various intensities are represented by orderly and, for most intensities, periodic, spatial patterns of distributed neuronal activity along an isofrequency strip. For low--to--moderate intensities, the mean relative activity along the entire isofrequency strip increases rapidly with intensity, with the spatial pattern of activity remaining quite constant along the strip. At higher intensities, however, the mean relative activity along the strip remains fairly constant with changes in intensity, but the spatial patterns change markedly. As a consequence of these effects, low- and high-intensity tones are represented by complementary distributions of activity alternating along an isofrequency strip. We conclude that in AI tone intensity is represented by two complementary modes, viz. discharge rate and place. Furthermore, the magnitude of the overall changes in the representation of tone intensity in AI appears to be closely related to psychophysical measures of loudness and of intensity discrimination.


Increased insulin sensitivity in iron-deficient rats.
Iron deficient (ID) and control (C) rats were studied to determine if severe iron deficiency alters insulin-stimulated glucose disposal. Euglycemic hyperinsulinemic glucose clamps were conducted by infusing insulin (2 m mu.kg-1.min-1, constant rate) for 120 min while maintaining euglycemia. In a 12-h fasted state, ID rats were hyperglycemic (109.4 +/- 4.0 mg.dL-1 arterial plasma glucose, x +/- SEM) when compared with C rats (86.9 +/- 3.4 mg.dL-1) (P less than 0.05). Even though insulin was infused identically on a per kilogram body weight basis for both groups, the resulting hyperinsulinemia was higher in ID rats (3.1 +/- 0.27 ng.mL-1) compared with C rats (2.3 +/- 0.4 ng.mL-1) at the end of the clamp. Glucose infusion rates required to maintain euglycemia were twofold higher in ID rats (27.0 +/- 5.4 mg.kg-1.min-1) versus C rats (13.1 +/- 3.3 mg.kg-1.min-1) (P less than 0.05). Circulating lactic acid increased in both groups, and the concentrations in ID rats (3.2 +/- 0.4 mmol.L-1) were significantly higher than those in C rats (1.8 +/- 0.5 mmol.L-1) at the end of the clamp. When the efficiency of insulin to dispose glucose was evaluated by calculating the glucose disposal divided by the prevailing insulinemia, ID rats could dispose of almost twice the glucose per unit of insulin [9.0 +/- 0.6 (mg.kg-1.min-1)/(ng.mL-1)] when compared with C rats [5.6 +/- 0.9 (mg.kg-1.min-1)/(ng.mL-1)] (P less than 0.05). The data indicate that insulin sensitivity is increased in ID rats and that ID rats cannot metabolize exogenous insulin as well as C rats.


[Relationship between central obesity and clustering of cardiovascular risk factors in adults of Jiangsu province].
To explore the relationship between central obesity and cardiovascular risk factors and their clustering in adults of Jiangsu province. Multi-stratified clustering sampling method was used to sample 8 400 residents aged 18 years and over from 14 diseases surveillance units in Jiangsu province from October to December 2010. Information was obtained with face-to-face interview, physical examination and laboratory testing. A total of 8 380 residents finished the study protocol and their data were analyzed. Central obesity was defined as waist circumference ≥ 85 cm in males or ≥ 80 cm in females. Following complex weighting of the samples, level and proportion of cardiovascular risk factors in group with different waist circumference were analyzed. The prevalence of central obesity among adults in Jiangsu province was 46.2%, the proportion of males and females was 46.4% and 46.1%, respectively (P > 0.05). The prevalence of center obesity varied significantly in residents with different age, area, education and occupation (all P < 0.01). The level of systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, high density lipoprotein cholesterol and low density lipoprotein cholesterol was also significantly different in residents with different degree of waist circumference (all P < 0.01). The prevalence of hypertension, diabetes, dyslipidemia and clustering of cardiovascular risk factors increased in proportion to increasing waist circumference (all P < 0.05). Multivariate logistic regression analysis showed that the risk of hypertension, diabetes, dyslipidemia and clustering of cardiovascular risk factors was 2.2 (OR = 2.2, 95% CI: 2.0-2.4) and 4.7 (OR = 4.7, 95% CI: 3.9-5.7); 2.1 (OR = 2.1, 95% CI: 1.7-2.5) and 3.8 (OR = 3.8, 95% CI: 3.2-4.5); 2.3 (OR = 2.3, 95% CI: 1.8-2.9) and 4.1 (OR = 4.1, 95% CI: 3.2-5.3); 3.4 (OR = 3.4, 95% CI: 2.9-3.9) and 8.0 (OR = 8.0, 95% CI: 6.2-10.2) fold higher in residents with mild and severe central obesity than residents without central obesity. The extent of central obesity positively correlates with the prevalence of cardiovascular risk factors and their clustering in adults of Jiangsu province. Comprehensive interventions on obesity serve as an important tool to reduce the cardiovascular risk in adult Jiangshu residents.


SOx storage materials under Lean-Rich cycling conditions--Part II: influence of Pt, H2O, and cycling time.
The role of Pt and the influence of the reaction conditions during lean-rich cycling experiments were studied on a second generation SOx trapping material. The combination of the Generalized 2-D Correlation Analysis, 2-D Sample-Sample Correlation Analysis, and Factor Analysis using the MCR-ALS technique was applied to identify the reactive species. Transient surface sulfate species were formed under oxidative reaction conditions (lean mode) and decomposed under reducing reaction conditions (rich operation mode). The reduction of this species was identified to be the main contribution to the SO2 release observed under dynamic flow conditions. Pt facilitates the formation of sulfates but also catalyzes the reduction of the transient surface sulfate species leading to a higher amount of SO2 released under rich conditions. In the presence of water, this effect was diminished, which was found to be mainly a result of the suppressed formation of surface sulfate species caused by the faster transport of SO2 into the bulk phase of the SOx trapping component (BaCO3). Increasing the time under reducing conditions in the cycles leads to an enhanced reduction of the surface during rich conditions. The presence of water did not influence the bulk type species. It is proposed that for effective SO2 storage materials, strong SOx adsorption sites on the surface, the presence of water, and a short time under reducing conditions are essential.


Cancer incidence and survival in patients 65 years of age and older.
The impact of cancer on persons 65 years of age and older has been assessed by examining incidence rates and survival rates. For all cancers combined, the incidence rate shown in Table 4 for males 65 and older (2,468.2 per 100,000) is four times the age-adjusted rate for males 45 to 64 years of age (586.7). For elderly females, the incidence rate is twice that for females aged 45 to 64 (1,401.1 versus 609.7). Ratios of incidence rates for older versus younger males are about four to five for cancers of the stomach, colon, rectum, pancreas, and urinary bladder, and for leukemia; about three for cancers of the lung and kidney, and for non-Hodgkin's lymphomas; and 10 for cancer of the prostate. For females, the corresponding ratios are similar to those for males, although a little lower for cancers of the colon, rectum, and urinary bladder, and for leukemia, and a little higher for cancers of the stomach and pancreas. The ratios for breast, uterine cervix, uterine corpus, ovary, and lung are less than two. The relative survival rates for patients 65 and older are for many cancer sites only a few percentage points lower than rates for those 45 to 64 years of age (Table 5), suggesting that patients in this age group fare only a little worse than younger patients in escaping the effects of cancer once it has been diagnosed. Exceptions are cancer of the urinary bladder and non-Hodgkin's lymphomas for both men and women and cancers of the uterine cervix, uterine corpus, ovary, and kidney for women. For these sites, the survival rates for older patients are considerably lower than for their younger counterparts. For female breast cancer patients, there was no difference in the five-year relative survival rate for those 65 and older compared with those 45 to 64.


Properties of an αs-casein-rich casein fraction: influence of dialysis on surface properties, miscibility, and micelle formation.
In this study, the surface tension, miscibility, and particle size distribution of a solution containing an αs-casein (CN)-rich CN fraction (54 wt % αs-CN, 32 wt % β-CN, and 15 wt % κ-CN) were determined at pH 6.6. The nondialyzed CN fraction was compared with a dialyzed one. In the nondialyzed sample, every charge on the protein was compensated by 0.3 charges coming from counterions, whereas in the dialyzed sample, only 0.2 charges could be assigned to each charge on the protein. This relation was determined by calculating the charges at the proteins, taking the measured mineral content into account. The surface tension was measured as a function of the protein concentration by the du Noüy ring method at room temperature. Results indicated alterations in the surface properties after reduction of counterions. The equilibrium surface tension above the critical micelle concentration increased from 40.1×10(-3) to 45×10(-3) N/m, the critical micelle concentration increased from 0.9×10(-4) to 2×10(-3) mol/L, and the minimal area occupied per molecule at the surface increased from 2.4×10(-18) to 4.6×10(-18) m(2). Cloud points were determined by measuring the absorbance of CN solutions as a function of the temperature. The cloud points were found to be concentration dependent and had a minimum at 0.2 wt % at 34°C for nondialyzed CN and at 0.25 wt % at 28°C for dialyzed CN, again demonstrating the influence of counterion reduction. Below the cloud point, a micellar phase was found to exist. The hydrodynamic diameter of the micelles were characterized by dynamic light scattering in both auto- and cross-correlation mode. However, no influence of reduction in counterions could be observed, possibly due to the fact that dynamic light scattering is not a suitable method for this type of system. The presence of self-assembled structures was verified by freeze-fracture electron microscopy. The observed differences between dialyzed and nondialyzed samples were explained by changes in the counterion cloud surrounding the proteins. Consequently, the electrostatic interactions between as well as within the CN are altered by dialysis, which, in turn, affects the behavior at the surface as well as the properties in the solution.


[Identification of Complex and Combined Antibody Consisted of Anti-c, Anti-E, Anti-Jka and Anti-Fya].
To investigate the role of multiple serological methods in the identification of complex antibodies. The blood group antigens were detected by saline and microcolumn agglutination methods. The saline method was used to screen and identify IgM-type antibodies in the patient's serum, while the polybrene, anti-globulin, microcolumn agglutination, enzymic and absorption-elution methods were used to screen and identify IgG-type antibodies. The patient was B/CCDee/Jk(a-b+)/Fy(a-b+) blood type. The serum reacted with panel cells, and the reaction presented anti-E pattern in the saline medium. It was fully positive in the microcolumn agglutination card, except 2 negative ones after using papain to treat the panel cells. Referring to the pattern table, it was concluded that there existed anti-c, anti-E, and anti-Jka antibodies, and one antibody corresponding to an antigen that was easily destroyed by papain. The red blood cells with specific phenotype were selected for absorption-elution to identify IgG-type anti-c, anti-E, anti-Jka and anti-Fya antibodies. It is confirmed that IgM-type anti-E, and IgG-type anti-c, anti-E, anti-Jka and anti-Fya antibodies exist in the patient's serum by multiple serological methods.


[Learning doctor-patient communication: does co-teaching help?].
The first part of the medical interview is perhaps one of the most significant components of the doctoras role. How to collect relevant information and how to build a therapeutic relationship with the patient must be taught during the undergraduate curriculum. Clinical teachers have little experience in the teaching skills required to help students learn about doctor-patient communication. To measure outcomes and perceptions of using a co-teaching model in a course on interviewing during the third year of medical school in the Pontificia Universidad Católica de Chile. A mixed methods controlled study in which the intervention group participated in a co-teaching workshop with a clinical teacher and a specialist in doctor-patient communication skills (SDPC). The control group participated in a workshop with one clinical teacher. All students completed a questionnaire measuring perception of their learning in communication skills. Semi-structured interviews were used to collect the clinical teachers' perception. At the end of the course, the clinical and communication skills of all the students were measured in an objective structured clinical examination. Students and teachers agreed that co-teaching allows greater emphasis and practice in communication skills. The results of the objective structured clinical examination show that despite this greater emphasis, no deleterious effect on the clinical skills was demonstrated during the exam. The use of co-teaching in a course on interviewing allows students to perceive a higher level of learning in communication skills, and possibly enhances their skills. The clinical teachers felt that the co-teacher was an important support.


Oral (drinking water) two-generation reproductive toxicity study of bromodichloromethane (BDCM) in rats.
Bromodichloromethane (BDCM) was tested for reproductive toxicity in a two-generation study in CRL SD rats. Thirty rats/sex/ group/generation were continuously provided BDCM in drinking water at 0 (control carrier, reverse osmosis membrane-processed water), 50,150, and 450 ppm (0, 4.1 to 12.6, 11.6 to 40.2, and 29.5 to 109.0 mg/kg/day, respectively). Adult human intake approximates 0.8 microg/kg/day (0.0008 mg/kg/day). P and F1 rats were observed for general toxicity (viability, clinical signs, water and feed consumption, body weights, organ weights [also three weanling Fl and F2 pups/sex/litter], histopathology [10/sex, 0- and 450-ppm exposure groups]) and reproduction (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios, viabilities, maternal behaviors, reproductive organ weights [also three weanling Fl and F2 pups/sex/ litter], sperm parameters, and implantations. F1 rats were evaluated for age at vaginal patency or preputial separation. Ten P and F1 rats/sex from the 0- and 450-ppm exposure groups and rats at 50 and 150 ppm with reduced fertility were evaluated for histopathology (gross lesions, testes, intact epididymis, all F1 dams for number of primordial follicles). Developmental parameters in offspring included implantation and pup numbers, sexes, viabilities, body weights, gross external alterations, and reproductive parameters (Fl adults). Toxicologically important, statistically significant effects at 150 and/or 450 ppm included mortality and clinical signs associated with reduced absolute and relative water consumption, reduced body weights and weight gains, and reduced absolute and relative feed consumption (P and F1 rats). Significantly reduced body weights at 150 and 450 ppm were associated with reduced organ weights and increased organ weight ratios (% body and/or brain weight). Histopathology did not identify abnormalities. Small delays in sexual maturation (preputial separation, vaginal patency) and more Fl rats with prolonged diestrus were also attributable to severely reduced pup body weights. Mating, fertility, sperm parameters, and primordial ovarian follicular counts were unaffected. The no-observable-adverse-effect level (NOAEL) and the reproductive and developmental NOAELs for BDCM were at least 50 ppm (4.1 to 12.6 mg/kg/day), 5125 to 15,750 times the human adult exposure level, if delayed sexual maturational associated with severely reduced body weights is considered reproductive toxicity. If considered general toxicity, reproductive and developmental NOAELs for BDCM are greater than 450 ppm (29.5 to 109.0 mg/kg/day), or 36,875 to 136,250 times the human adult exposure level. Regardless, these data indicate that BDCM should not be identified as a risk to human reproductive performance or development of human conceptuses.


Computed tomography correlation of skeletal landmarks and vascular anatomy in civilian adult trauma patients: Implications for resuscitative endovascular balloon occlusion of the aorta.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a valuable resuscitative adjunct in a variety of clinical settings. In resource-limited or emergency environments, REBOA may be required with delayed or absent image-guidance or verification. Catheter insertion lengths may be informed by making computed tomography (CT) correlations of skeletal landmarks with vascular lengths. Between 2000 and 2015 at a single civilian tertiary care center, 2,247 trauma patients with CT imaging were identified, yielding 1,789 patients with adequate contrast opacification of the arterial system in the chest, abdomen, and pelvis. Individual scans were analyzed using MATLAB software, with custom high-throughput image processing algorithms applied to correlate centerline vascular anatomy with musculoskeletal landmarks. Data were analyzed using R version 3.3. The median centerline distance from the skin access to the aortic bifurcation was longer by 0.3 cm on the right than on the left side. Median aortic zone I length was 21.6 (interquartile range, 20.3-22.9) cm, while zone III was 8.7 (7.8-9.5) cm. Torso extent (TE) correlation to zone I was much higher than that for zone III (R2, 0.58 vs. 0.26 (right) and 0.58 vs. 0.27 (left); p < 0.001). Assuming a 4-cm balloon length, optimal fixed insertion length would be 48 cm and 28 cm for zones I and III (error, 0.4% vs. 33.3%), respectively, although out of zone placements can be reduced if adjusted for TE (error, 0% vs. 26.4%). Computed tomography morphometry suggests that a fixed REBOA catheter insertion length of 48 cm for zone I and 28 cm for zone III is optimal (on average, for average-height individuals), with improved accuracy by formulaic adjustments for TE. High residual error for zone III placement may require redesign of existing catheter balloon lengths or consideration of the relative risk associated with placing the balloon catheter too low or too high. Prognostic/epidemiological, level III.


Helicase-AID: A novel molecular device for base editing at random genomic loci.
CRISPR-enabled deaminase base editing has become a powerful tool for precisely editing nucleotides on the chromosome. In this study DNA helicases, such as Escherichia coli DnaB, were fused to activation-induced cytidine deaminase (AID) to form enzyme complexes which randomly introduces edited bases throughout the chromosome. DnaB-AID was found to increase 2.5 × 103 fold relative to the mutagenesis frequency of wildtype. 97.9% of these edits were observed on the leading strand during DNA replication suggesting deamination to be highly coordinated with DNA replication. Using DnaB-AID, a 371.4% increase in β-carotene production was obtained following four rounds of editing. In Saccharomyces cerevisiae Helicase-AID was constructed by fusing AID to one of the subunits of eukaryotic helicase Mcm2-7 complex, MCM5. Using MCM5-AID, the average editing efficiency of five strains was 2.1 ± 0.4 × 103 fold higher than the native genomic mutation rate. MCM5-AID was able to improve β-carotene production of S. cerevisiae 4742crt by 75.4% following eight rounds of editing. The S. cerevisiae MCM5-AID technique is the first biological tool for generating and accumulating single base mutations in eukaryotic chromosomes. Since the helicase complex is highly conservative in all eukaryotes, Helicase-AID could be adapted for various applications and research in all eukaryotic cells.


Identification of QTLs for root characteristics in maize grown in hydroponics and analysis of their overlap with QTLs for grain yield in the field at two water regimes.
We investigated the overlap among quantitative trait loci (QTLs) in maize for seminal root traits measured in hydroponics with QTLs for grain yield under well-watered (GY-WW) and water-stressed (GY-WS) field conditions as well as for a drought tolerance index (DTI) computed as GY-WS/GY-WW. In hydroponics, 11, 7, 9, and 10 QTLs were identified for primary root length (R1L), primary root diameter (R1D), primary root weight (R1W), and for the weight of the adventitious seminal roots (R2W), respectively. In the field, 7, 8, and 9 QTLs were identified for GY-WW, GY-WS, and DTI, respectively. Despite the weak correlation of root traits in hydroponics with GY-WW, GY-WS, and DTI, a noticeable overlap between the corresponding QTLs was observed. QTLs for R2W most frequently and consistently overlapped with QTLs for GY-WW, GY-WS, and/or DTI. At four QTL regions, an increase in R2W was positively associated with GY-WW, GY-WS, and/or DTI. A 10 cM interval on chromosome 1 between PGAMCTA205 and php20644 showed the strongest effect on R1L, R1D, R2W, GY-WW, GY-WS, and DTI. These results indicate the feasibility of using hydroponics in maize to identify QTL regions controlling root traits at an early growth stage and also influencing GY in the field. A comparative analysis of the QTL regions herein identified with those described in previous studies investigating root traits in different maize populations revealed a number of QTLs in common.


Protective immunity of E. coli-synthesized NS1 protein of Japanese encephalitis virus.
Immunogenicity and protective efficacy of recombinant Japanese encephalitis virus (JEV) NS1 proteins generated using DNA vaccines and recombinant viruses have been demonstrated to induce protection in mice against a challenge of JEV at a lethal dose. The West Nile virus NS1 region expressed in E. coli is recognized by these protective monoclonal antibodies and, in this study, we compare immunogenicity and protective immunity of the E. coli-synthesized NS1 protein with another protective immunogen, the envelope domain III (ED3). Pre-challenge, detectable titers of JEV-specific neutralizing antibody were detected in the immunized mice with E. coli-synthesized ED3 protein (PRNT50 = 1:28) and the attenuated JEV strain T1P1 (PRNT50 = 1:53), but neutralizing antibodies were undetectable in the immunized mice with E. coli-synthesized NS1 protein (PRNT50 < 1:10). However, the survival rate of the NS1-immunized mice against the JEV challenge was 87.5% (7/8), showing significantly higher levels of protection than the ED3-immunized mice, 62.5% (5/8) (P = 0.041). In addition, E. coli-synthesized NS1 protein induced a significant increase of anti-NS1 IgG1 antibodies, resulting in an ELISA titer of 100,1000 in the immunized sera before lethal JEV challenge. Surviving mice challenged with the virulent JEV strain Beijing-1 showed a ten-fold or greater rise in IgG1 and IgG2b titers of anti-NS1 antibodies, implying that the Th2 cell activation might be predominantly responsible for antibody responses and mice protection.


Histone deacetylase inhibitors: the Abbott experience.
Histone deacetylase inhibitors have generated significant interest as anti-cancer agents due to their ability to cause growth arrest, terminal differentiation and/ or apoptosis in carcinoma cells. Abbott entered this area after the serendipitous discovery of the biaryl hydroxamate A-161906 in a TGF beta mimetic screen and the subsequent identification of this compound as an inhibitor of selected HDACs. The complex biology of these enzymes became evident when cloning and expression of the HDACs demonstrated that they were present as multiprotein and, in some cases, multi-HDAC containing complexes in their active forms. This discovery suggested that any selectivity determinations would have to be considered in the context of these multi-protein/HDAC complexes. However, siRNA gene knockdown studies did demonstrate that reduction of the Class I HDACs resulted in a phenotype similar to that observed with small molecule HDAC inhibitors. Evaluation of the Abbott small molecule HDAC inhibitors utilized a Class I HDAC (HDAC 1/2) preparation and antiproliferation assays using HT1080 fibrosarcoma and MDA435 breast carcinoma cells. Characterization of several series of hydroxamic acids indicated that while many of these analogs possessed potent enzymatic and cellular activity, in general these compounds had unacceptable pharmacokinetic profiles and marginal antitumor effects. Replacement of the potentially labile hydroxamic acid moiety with a trifluoromethyl ketone or a ketooxazole gave measurable HDAC potency but only modest cellular and in vivo activity. However, hydroxamate replacement with an alpha-ketoamide moiety provided potent HDAC inhibitors (IC(50) values as low as 3 nM) with excellent cellular activity (IC50 values < 0.2 microM) and measurable anti-tumor activity in a flank tumor growth model.


Synthesis and structure-active relationship of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline anticonvulsants.
We have previously disclosed that some 6,7-dimethoxyisoquinoline derivatives are able to produce anticonvulsant effects in different animal models of epilepsy. Following these studies this paper describes the synthesis of a small series of new 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines strictly related to previously reported analogues. This novel series of isoquinolines was designed on the basis of well defined structure-active relationship (SAR) information already acquired for this class of anticonvulsant agents. The pharmacological effects of the new synthesized compounds were evaluated against audiogenic seizures in Dilute Brown non-Agouti (DBA/2) mice. The preliminary pharmacological screening led to the identification of a new active molecule the 2-acetyl-1-(4'-methylphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6d) that displayed significant anticonvulsant activity. Computational studies helped to rationalize these obtained pharmacological results.


Identification and comparison of the 3 early stages of resynthesis for the lichen Cladonia rangiferina.
A lichen is an association between a biotrophic fungal partner and a green algal and (or) cyanobacterial partner, which may be considered a "controlled" parasitic interaction. While controlled parasitism implies benefit to both interacting partners, a parasitism that is not controlled implies that one partner benefits to the detriment of the other partner. The objective of this study was to compare morphological development of the interaction between Cladonia rangiferina with its compatible algal partner (Asterochloris glomerata/irregularis) and incompatible algae (Coccomyxa peltigerae and Chloroidium ellipsoideum) at 3 early resynthesis stages. The fungus was co-inoculated with each alga separately and the stages of development were compared using quantitative measures. The first 3 stages of development of the lichen thallus were identified in the compatible interaction as the "pre-contact" stage (1 day post co-inoculation (PCI)), "contact" stage (8 days PCI), and "growth together" stage (21 days PCI). Compatible interactions showed significantly shorter internode length, significantly more new lateral hyphal branches, significantly greater appressorial frequency, and no reduction in cell diameter of the algal cells, compared with incompatible interactions. At 21 days PCI, a parasitic interaction was observed between Cladonia rangiferina and Chloroidium ellipsoideum. These findings support the importance of recognition between compatible partners for successful lichenization. This study also revealed a strategy that may explain the success of this species in northern habitats. Identification of the resynthesis stages of Cladonia rangiferina is required before expression of the proteins involved in recognition and defense can be understood.


Autofluorescence bronchoscopy, a novel modality for the early detection of bronchial premalignant and malignant lesions.
Lung cancer is the leading cause of cancer deaths in developed countries. Recently, autofluorescence bronchoscopy has been reported to improve the early detection of lung cancer in high-risk individuals. In the present study, we evaluated the efficacy of autofluorescence bronchoscopy for the early detection of bronchial premalignant and malignant lesions. From November 2000 through March 2004, 123 high-risk individuals (114 men and 9 women with a mean age of 68 years) were enrolled. Among 282 biopsy specimens, 93 (33.0%) were premalignant or malignant lesions. The sensitivity and negative predictive value for the detection of bronchial premalignant and malignant lesions were significantly higher with the addition of autofluorescence bronchoscopy than white light bronchoscopy alone. Moreover, the sensitivity for the detection of bronchial premalignant lesions was extremely higher with the addition of autofluorescence bronchoscopy than white light bronchoscopy alone, whereas there was no significant difference between autofluorescence bronchoscopy and white light bronchoscopy alone for the detection of non-malignant and malignant lesions. Autofluorescence bronchoscopy is a novel modality for the early detection of bronchial abnormality, especially for bronchial premalignant lesions.


Virulence genes, Shiga toxin subtypes, major O-serogroups, and phylogenetic background of Shiga toxin-producing Escherichia coli strains isolated from cattle in Iran.
The aim of this study was to investigate the virulence potential of the isolated bovine STEC for humans in Iran. In this study a collection of STEC strains (n = 50) had been provided via four stages, including sampling from feces of cattle, E. coli isolation, molecular screening of Shiga toxin (stx) genes, and saving the STEC strains from various geographical areas in Iran. The STEC isolates were subjected to stx-subtyping, O-serogrouping, and phylo-grouping by conventional polymerase chain reaction (PCR). Occurrence of stx1 (52%) and stx2 (64%) was not significantly different (p = 0.1), and 16% of isolates carried both stx1 and stx2, simultaneously. In addition, 36% and 80% of the isolates were positive for eae and ehxA, respectively. Molecular subtyping showed that stx1a (52%), stx2a (44%), stx2c (44%), and stx2d (30%) were the most prevalent subtypes; two combinations stx2a/stx2c and stx2c/stx2d coexisted in 18% and 10% of STEC strains, respectively. Three important non-O157 serogroups, including O113 (20%), O26 (12%), and O111 (10%), were predominant, and none of the isolates belonged to O157. Importantly, one O26 isolate carried stx1, stx2, eae and ehxA and revealed highly virulent stx subtypes. Moreover, all the 21 serogrouped strains belonged to the B1 phylo-type. Our study highlights the significance of non-O157 STEC strains carrying highly pathogenic virulence genes in cattle population as the source of this pathogen in Iran. Since non-O157 STEC strains are not routinely tried in most diagnostic laboratories, majority of the STEC-associated human infections appear to be overlooked in the clinical settings.


Liquid Crystalline Granules Align in a Hierarchical Structure To Produce Spider Dragline Microfibrils.
The spider silk spinning process converts spidroins from an aqueous form to a tough fiber. This spinning process has been investigated by numerous researchers, and micelles or liquid crystals of spidroins have been reported to form silk fibers, which are bundles of silk microfibrils. However, the formation process of silk microfibrils has not been clarified previously. Here, we report that silk microfibrils are generated through the formation, homogenization, and linkage of liquid crystalline granules without micelle-like structures. Heterogeneous granules on the submicron to micron scale were observed in the storage sac, whereas homogeneous granules with diameters of approximately 100 nm were aligned along the tapering duct. In the spun fibers, the homogeneous granules were connected along the fiber axis. This is the first clear description of the formation of granule-based microfibrils in the spinning process, which is the key conversion process leading to the unique hierarchical structure of spider dragline.


The association between the severity of anemia and socio-demographic factors among children under five years of age in Kut City.
Anemia is a public health issue that affects both industrialized and developing nations. Childhood anemia has severe consequences, including reduced growth, poor motor and cognitive development, and increased death and morbidity. This study aims to determine sociodemographic factors associated with the severity of anemia among under-five children in Kut City. A cross-sectional study with a convenience sample (non-probability) was conducted among 264 children admitted to hospitals in Kut City, from September 1st, 2022, to March 1st, 2023. Data were collected via questionnaires, and descriptive and inferential statistics were used to evaluate the data. The total number of children participating in the study was 264, with 39.0% having mild anemia and 60.0% having moderate anemia, according to the World Health Organization classification of anemia. The results showed that the children most at risk of developing anemia were within 4 years of age and had a lower mean hemoglobin level than the rest of the age groups of the children participating in the study, compared to the mean+standard deviation (SD) (9.46+0.99). Boys are more affected than girls, and those who reside in rural areas have lower hemoglobin (HB) percentages with a mean+SD of (9.21+0.93). Unemployed mothers who read and write had the lowest HB percentage. In contrast, parents with primary education and government jobs have the lowest percentage of HB. Children of married mothers are more affected by anemia. Families with high overcrowding showed the lowest rate of HB. They experienced low socioeconomic status as a result. The degree of anemia was significantly correlated with the child's age, residence, mother's educational level, father's job, and socioeconomic position. This study concludes a significant association between the severity of anemia and sociodemographic factors, both unmodifiable (age) and modifiable (residence, mothers' education, fathers' jobs, and economic and social status). Children with modifiable risk factors need to have their anemia risk constantly evaluated.


Narrowband terahertz generation with chirped-and-delayed laser pulses in periodically poled lithium niobate.
We generate narrowband terahertz (THz) radiation in periodically poled lithium niobate (PPLN) crystals using two chirped-and-delayed driver pulses from a high-energy Ti:sapphire laser. The generated frequency is determined by the phase-matching condition in the PPLN and influences the temporal delay of the two pulses for efficient terahertz generation. We achieve internal conversion efficiencies up to 0.13% as well as a record multicycle THz energy of 40 μJ at 0.544 THz in a cryogenically cooled PPLN.


An ACCESS-based academic attending physician and resident rotation evaluation database.
A database of residents' evaluations of their Internal Medicine (IM) rotations and attending physicians (APs) was created using ACCESS (Microsoft). The IM attendings and the corresponding inpatient or outpatient rotations from three academic settings (county hospital, VA, and University) are ranked by 130 different residents. For APs, reports show rotation specific, year average and, for comparison, all-AP aggregate values. For rotations, reports provide estimates of workload, didactic teaching, and overall desirability. Free text comments may be provided for all evaluations.


Residual dynamic and risk assessment of dimethomorph in Swiss chard grown at two different sites.
Residue analysis of dimethomorph in Swiss chard cultivated at two different locations under greenhouse conditions was conducted using high-performance liquid chromatography-ultraviolet detection and confirmed by tandem mass spectrometry. The randomly collected samples (over 14 days) were extracted with acetonitrile and purified using a Florisil solid-phase extraction cartridge. Linearity over a concentration range of 0.05-50.0 mg/L had an excellent coefficient of determination of 0.9996. Recovery rate ranged from 82.98 to 95.43% with relative standard deviations ≤5.12% and limits of detection and quantification of 0.003 and 0.01 mg/kg, respectively. The initial deposits [day 0 (2 h post-application)] were considerably lower (7.57 and 8.55 mg/kg for sites 1 and 2, respectively) than the maximum residue limit (30 mg/kg) set by the Korean Ministry of Food and Drug Safety. The dissipation half-life was approximately the same, being 5.0 and 5.1 days for sites 1 and 2, respectively. Risk assessment estimated as acceptable daily intake revealed a value of 0.084 or 0.094% (day 0) and 0.014% (10 days post-application), for sites 1 and 2, respectively. The values indicated that dimethomorph can be safely used on Swiss chard, with no hazardous effects expected for Korean consumers.


C-Terminal properties are important for ring-fused 2-pyridones that interfere with the chaperone function in uropathogenic E. coli.
Virulence-associated organelles, termed pili or fimbriae, are assembled via the highly conserved chaperone-usher pathway in a vast number of pathogenic bacteria. Substituted bicyclic 2-pyridones, pilicides, inhibit pilus formation, possibly by interfering with the active site residues Arg8 and Lys112 of chaperones in uropathogenic E. coli. In this article we describe the synthesis and evaluation of nine analogues of a biologically active pilicide. Derivatization was performed with respect to its C-terminal features and the affinities for the chaperone PapD were studied with 1H relaxation-edited NMR spectroscopy. It could be concluded that the carboxylic acid functionality and also its spatial location was important for binding. In all cases, binding was significantly reduced or even abolished when the carboxylic acid was replaced by other substituents. In addition, in vivo results from a hemagglutination assay are presented where the derivatives have been evaluated for their ability to inhibit pilus formation in uropathogenic E. coli.


Patterns of childhood maltreatment and intimate partner violence, emotion dysregulation, and mental health symptoms among lesbian, gay, and bisexual emerging adults: A three-step latent class approach.
Childhood abuse and neglect (CAN) and intimate partner violence victimization (IPV) is prevalent among lesbian, gay, and bisexual individuals (LGB). Identification of distinct patterns of childhood and adult victimization, including technology-mediated and face-to-face IPV, and their cumulative relations to mental/behavioral health challenges, among LGB people is needed to facilitate identification of at-risk individuals. Using latent class analysis, we first sought to identify patterns of lifetime interpersonal victimization, primarily five types of CAN and IPV in LGB emerging adults. Second, we examined if LGB-status and race/ethnicity predicted class-membership; third, we assessed differences between the latent classes on emotion dysregulation, depressive and anxiety symptoms, and alcohol use. Participants were 288 LGB adults between 18-29 years (M = 25.35, SD = 2.76; 41.7% gay/lesbian) recruited via Amazon MTurk. The 3-step LCA identified five-latent classes: high victimization, childhood emotional abuse and neglect, cybervictimization, adult face-to-face IPV, and lower victimization. People of color (including Hispanics) were more likely to be in the high victimization class, and bisexual individuals, especially bisexual women, in the childhood emotional abuse and neglect class. High victimization and childhood emotional abuse and neglect classes had elevated emotion dysregulation levels and depression and anxiety symptoms, and the high victimization class reported the highest levels of alcohol use. Findings suggest a detrimental effect of cumulative interpersonal victimization on emotion dysregulation and the mental/behavioral health of LGB emerging adults, with bisexuals and LGB-people of color at heightened risk of cumulative victimization and of related mental/behavioral health challenges.


The recall of digits by normal, deaf and autistic children.
Normal, autistic and deaf children were tested for their immediate memory of visually presented digits. The digits were exposed either with or without a left to right spatial display arrangement, and had to be recalled forewards as well as backwards. Normal and deaf children tended to be sensitive to both display conditions and recall requirements whereas autistic children were mainly affected by direction of recall. Serial position effects in the normal and deaf groups were more dependent on order of retrieval than on input order.


[Development of theophylline in treatment of asthma and chronic obstructive pulmonary disease].
Theophylline has been reduced usage in asthma and chronic obstructive pulmonary disease because of the high frequency of side effects and the relatively low efficacy. However, recent researches have demonstrated that low-dose theophylline can not only relax airway smooth muscle but also have anti-inflammatory or immunomodulatory actions, which provides theory basis for the treatment of asthma and chronic obstructive pulmonary disease.


Genotypic variation in rice yield enhancement by elevated CO2 relates to growth before heading, and not to maturity group.
Maturity group (based on the number of days to maturity) is an important growth trait for determining crop productivity, but there has been no attempt to examine the effects of elevated [CO(2)] on yield enhancement of rice cultivars with different maturity groups. Since early-maturing cultivars generally show higher plant N concentration than late-maturing cultivars, it is hypothesized that [CO(2)]-induced yield enhancement might be larger for early-maturing cultivars than late-maturing cultivars. To test this hypothesis, the effects of elevated [CO(2)] on yield components, biomass, N uptake, and leaf photosynthesis of cultivars with different maturity groups were examined for 2 years using a free-air CO(2) enrichment (FACE). Elevated [CO(2)] significantly increased grain yield and the magnitude significantly differed among the cultivars as detected by a significant [CO(2)] x cultivar interaction. Two cultivars (one with early and one with late maturity) responded more strongly to elevated [CO(2)] than those with intermediate maturity, resulting mainly from increases in spikelet density. Biomass and N uptake at the heading stage were closely correlated with grain yield and spikelet density over [CO(2)] and cultivars. Our 2 year field trial rejected the hypothesis that earlier cultivars would respond more to elevated [CO(2)] than later cultivars, but it is revealed that the magnitude of the growth enhancement before heading is a useful criterion for selecting rice cultivars capable of adapting to elevated [CO(2)].


Genetic and nongenetic factors influencing substance use by adolescents.
Substance use by adolescents can lead to mortality, physical and social morbidity, and a brain disorder called substance dependence if allowed to progress to chronic, repetitive self-administration. Substance abuse and dependence can begin in adolescence or adulthood, but many of the attitudes and behaviors that affect risk become established during adolescence. Genetic risk factors have been identified for at least two distinct disorders and more are under active study to determine the cause and pathophysiology of addictive disorders. Although much remains to be done, a complex interplay of numerous genetic and environmental risk factors clearly is involved. An understanding of the most important environmental risk factors has led to effective primary prevention approaches; knowledge of the genetic risk factors and neuropharmacology of drugs of abuse in the brain is beginning to influence secondary prevention efforts and treatment, including better medications for addictive disorders. A large proportion of adolescents carry a genetic vulnerability that can be expressed when they accept peer and societal influences that promote experimentation with substances of abuse. At that point, the genetic factors take over, maintaining the drug self-administration pattern. Decay of social status results from association with drug-using peers and shifts in priorities supportive of drug use rather than education and productivity. More research into the genetic risk factors and applications of current knowledge to treatment is needed.


Tissue distribution of RNAs for cystatins, histatins, statherin, and proline-rich salivary proteins in humans and macaques.
The tissue distribution of the mRNAs for a number of salivary proteins [proline-rich proteins (PRPs), statherin, cystatins, and the histatins] has been examined in humans and macaques in order to investigate their possible functions and tissue-specific regulation. We have shown that PRP RNAs (0.8-1.5 kb) are expressed in human and rhesus parotid and submandibular glands, and in the human bronchus. The genes for the acidic and basic PRPs are differentially regulated in these tissues. RNAs for acidic PRPs are predominantly expressed in the submandibular gland, for basic PRPs in the respiratory tract, and for both acidic and basic PRPs in the parotid gland. Protein studies of secretions from these tissues confirm the RNA results. Statherin RNA (0.65 kb) was detected in human and rhesus parotid and submandibular glands and the human bronchus, as well as in rhesus lacrimal glands. Statherin was found by tissue immunoperoxidase staining in the serous cells of respiratory tract submucosal glands, which is the same location for the synthesis of PRPs. Several cystatin RNAs (0.8-1.3 kb) were differentially expressed in human parotid glands, submandibular glands, and the bronchus, and in lacrimal glands from both rhesus and cynomolgus macaques. RNAs (0.6 kb) for the histatins were found only in parotid and submandibular glands. Thus, it appears that PRPs, statherin, and cystatins may play a broader role in the physiology of biological fluids and secretions than previously suspected, since they are found in secretions other than saliva. However, the functions of the histatins are restricted to saliva. These studies also pose some interesting questions regarding the differential expression of these genes in a variety of secretory tissues.


Research priorities child and maternal nutrition: a USAID perspective.
This paper presents the views of the United States Agency for International Development, India (USAID/India) on priorities for nutrition research in 2001-2005. Indices of nutrition status in India have been stagnant for 30 years. Although severe malnutrition has declined significantly, there has been little improvement since the 1970s in the percentage of children and/or mothers who are moderately undernourished. USAID views nutrition as a maternal and child survival intervention and focuses programmatic priorities on micronutrient nutrition (specifically vitamin A and iron/folate), integrated community nutrition (MinPak), and improved nutrition status through USAID's Title II program. Major areas of research interest for USAID include the prevalence and etiology of nutrition deficiencies, operations research to improve service delivery, the application of new tools and technologies to improve nutrition, and increasing the role of the private sector (including nongovernmental organizations) in nutrition service delivery. It is concluded that nutrition research must be prioritized to drive programmatic action; research must focus on the key questions; known tools must be widely applied; and elegance should be pursued in all research endeavors.


Optic lobe neurosecretory cells in Poekilocerus pictus (Orthoptera), Periplaneta americana (Dictyoptera), Belostoma indicum (Hemiptera), Polistes hebraeus (Hymenoptera) and Sandrocottus de jeani (Coleoptera).
Neurosecretory cells in the optic lobes of 5 insects viz. Poekilocerus pictus (Orthoptera), Periplaneta americana (Dictyoptera) Belostoma indicum (Hemiptera), Polistes hebraeus (Hymenoptera) and Sandrocottus dejeani(Coleoptera) have been described. They occur in the distal optic chiasma of the optic lobes in the form of a cone-shaped concentration with two arms, a dorsal and a ventral. The number of neurosecretory cells in the optic lobes varies from species to species viz., about 150 in Poekilocerus, 115 in Periplaneta, 45 in Belostoma, 90 in Polistes and 70 in Sandrocottus. They are mostly monopolar but occasionally bipolar and stain green with PAF and red or sometimes deep purple with Heidenhain's Azan technique. The axons of the monopolar cells run into the optic lobe or the brain, while those of the bipolar cells form a sort of two way connection one end going to the eye and the other to the brain. Neurosecretory cells in all the insects described above have synchronous secretory cycles.


Boron Nitride Nanosheet-Veiled Gold Nanoparticles for Surface-Enhanced Raman Scattering.
Atomically thin boron nitride (BN) nanosheets have many properties desirable for surface-enhanced Raman spectroscopy (SERS). BN nanosheets have a strong surface adsorption capability toward airborne hydrocarbon and aromatic molecules. For maximized adsorption area and hence SERS sensitivity, atomically thin BN nanosheet-covered gold nanoparticles have been prepared for the first time. When placed on top of metal nanoparticles, atomically thin BN nanosheets closely follow their contours so that the plasmonic hot spots are retained. Electrically insulating BN nanosheets also act as a barrier layer to eliminate metal-induced disturbances in SERS. Moreover, the SERS substrates veiled by BN nanosheets show an outstanding reusability in the long term. As a result, the sensitivity, reproducibility, and reusability of SERS substrates can be greatly improved. We also demonstrate that large BN nanosheets produced by chemical vapor deposition can be used to scale up the proposed SERS substrate for practical applications.


The influence of Hyssopus cuspidatus Boriss extract on lipid mediators metabolism network in asthmatic mice.
Current drugs do not provide an absolute cure or modify the course of asthma. Hyssopus cuspidatus Boriss extract (SXCF) has been used as Uyghur medicine for several years to treat bronchial asthma. However, very limited research has been conducted on the therapeutic mechanisms of SXCF. Disruptions in the metabolic network of lipid mediators (LMs) are closely linked to the development of asthma. Here, we explored the therapeutic mechanism of SXCF in asthma based on the metabolic network of LMs, aiming to contribute to the understanding of SXCF in asthma treatment at the molecular level. The UHPLC-MRM strategy was used for the quantitative detection of LMs in the lung tissue and in the peripheral circulatory system (serum). ELISA was used to detect IgE in serum and cytokines in BALF. The lung tissue sections were stained with H&E to observe the infiltration of inflammatory cells, and behavioural changes in mice were observed and recorded throughout the animal experiment. In contrast to the asthma group, the opposite result was observed in the SXCF groups, where the perturbed LMs metabolic network was partly restored in a dose-dependent manner with a significant elevation of anti-inflammatory metabolites, while pro-inflammatory lipids were decreased. As significant downregulation of IgE and pro-inflammatory cytokines was observed, IgE and cytokines analysis also supported the anti-inflammatory effects of SXCF. It was also noticed that SXCF treatment reduced the number of coughs and decreased the inflammatory cell infiltration around the bronchus in mice. These results suggested that SXCF has a significant ameliorative effect on ovalbumin (OVA)-induced asthma. The modulation of LMs is a possible underlying mechanism of the SXCF effects.